Despite the tremendous progress made in the field of biomedical engineering, many challenges still remain to be addressed—especially in the design of new materials. The biodegradable synthetic polymers currently used for biomedical applications are almost exclusively based on short aliphatic moieties, such as lactides, glycolides, ε-caprolactone, and sebacic acid, which all display relatively “hard” mechanical properties that adjust poorly to those of tissues, and therefore cause considerable stress mismatches at the inter-face responsible for necrosis or abnormal regeneration. [Wang et al., Nat. Biotechnol. 2002, 20, 602-606; Lendlein et al., Science 2002, 296, 1673-1676; and Park et al., Biomaterials: An Introduction, 2nd ed., Plenum, New York, 1992, pp. 1-6.]
In fact, most synthetic degradable biomaterials are based on aliphatic polyesters such as polylactides, polyglycolides and poly(ε-caprolactone). These materials can advantageously be functionalized or modified in order to be used in many biomedical applications. However, their mechanical properties are often inadequate for tissue engineering, especially that of soft tissues. For biomedical engineering, more precisely soft tissue engineering, it is indeed desirable to use materials with Young moduli matching those of the surrounding tissues.
In some cases, simple elasticity and suitable Young modulus are sufficient to allow soft tissue engineering. However, in other cases, more complex and smarter devices are required. Smart devices should enable an action of biological importance to be accomplished remotely in the body. The triggering stimulus could conveniently be the temperature and for many applications, the desired action is a change in shape. Shape memory is therefore a highly desirable characteristic for degradable materials aimed at biomedical applications.
Shape memory materials are materials that can be deformed, are capable to retain this deformed shape in some conditions and can then recover their original shape under an external stimulus such as the temperature. FIG. 1 shows a schematic representation of shape memory effect. In step 1, a deformation is applied to the object either by torsion, elongation, compression or any combination of these actions. The temporary shape of the object is retained either by quenching at low temperature or simply leaving the object below its transition temperature. In step 2, the permanent shape of the object is recovered by heating it above its transition temperature.
Typical known shape memory materials can be subdivided into two main classes: alloys, such as nitinol, and polymers, such as polyurethanes. Nitinol and various polyurethane shape memory polymers have been used for many applications ranging from inflatable reflectors for the aerospatial field to stents and stent-grafts.
Shape memory materials, whether alloys or polymers, have also been used in biomedical applications for a long time. Until very recently however, shape memory materials were non degradable. For biomedical applications, such materials stay in the body until they are removed during surgery. In many cases, it would be more advantageous and less invasive to use degradable shape memory polymers that do not require surgery to remove the implant.
Up to now, very few degradable shape memory materials have been developed and they are just starting to be used in biomedical studies. However, biomedical requirements, such as tunable transition temperature, Young modulus and hydrophilicity as well as an amorphous and thermoplastic nature and a controlled degradability are still not fully met in degradable shape memory materials developed so far.
For example, Lendlein and Langer developed degradable shape memory polymers a few years ago (U.S. Pat. No. 6,160,084). These materials are either thermosets or thermoplastic block copolymers. Thermosets are difficult to process and thermoplastics can display less heterogeneous degradation profiles as well as dramatic loss of mechanical properties upon degradation. Furthermore, it is still relatively difficult to control critical parameters such as the transition temperature, the Young modulus of the material or its hydrophilicity.
Some materials based on bile acids for drug delivery [Janout et al., J. Am. Chem. Soc. 2005, 127, 22-23; Janout et al., J. Am. Chem. Soc. 2000, 122, 2671-2672; and Virtanen et al., Eur. I. Org. Chem. 2004, 3385-3399] and controlled release [Gouin et al., Macromolecules 2000, 33, 5379] applications are known. However, reports on main-chain bile acid based polyesters, polyamides, and polyurethanes are still scarce in the literature, and their synthesis constitutes a real challenge, especially when higher molecular weights are required. However, up to now, the synthesis of such materials required using large amounts of coupling agents for the polycondensation reactions, which increased the toxicity of these materials.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.